Class Notes (835,600)
Canada (509,275)
Biology (6,794)

Section 6

6 Pages
Unlock Document

Biology 2382B
Sashko Damjanovski

SECTION 6 Membrane Proteins • With the exception of needing phospholipids to form semi- permeable closed compartments, membrane proteins carry out the biological functions of membranes. • Three types: 1. Integral 2. Lipid-linked 3. Peripheral • All are asymmetric Integral Membrane Proteins • Asymmetric – specifically oriented • Three distinct “domains”: o Cytoplasmic (hydrophilic) o Transmembrane (hydrophobic) o Exoplasmic (hydrophilic) • Transmembrane domain – hydrophobic secondary or tertiary structures that span the lipid bilayer • Different configurations – most common are the αhelices and β barrels • α helices (approx. 20-25 amino acids) • Arg and Lys (chargedAAs) near cytosolic side interact with polar head groups • Mostly glycosylated in exoplasmic domain (extracellular area) Lipid-Linked Proteins • Proteins that are linked to existing phospholipids in the bilayer • Proteins anchored to membrane by lipophilic adduct o Acylation of Gly residue of protein  Need N-terminal glycine  Linked to cytosolic side of the membrane o Prenylation of Cys residue of protein  Need C-terminal cysteine or cysteine close to C-terminal  Linked to cytosolic side of the membrane o Glycosylphosphatidylinositol (GPI) anchor  Needs phosphatidylinositol (one of the phospholipids)  Always on the exterior surface  With phosphatidylinositol, certain proteins can be linked  Recall: N-CAM is integral membrane protein – has all three domains and is involved in cell adhesion  But if N-CAM only has a GPI anchor, it can still be involved in cell adhesion, but it does not have cytoplasmic domain • Polypeptide chain (protein) does not enter bilayer • Has lateral mobility in membrane • Acylation attaches through N-terminal Gly residue • Prenylation attaches Cys residue at or near C terminus Peripheral Proteins • “Attached” through non-covalent interaction to either integral membrane proteins or lipid-linked proteins which are already linked to and part of the plasma membrane, through: o Ionic interactions, hydrogen bonds o Protein-protein interactions o van der Waals forces • Cytoskeletal filaments can associate with bilayer through peripheral proteins, as can ECM components o Depending on whether they are bound to integral membrane proteins or lipid-linked proteins Insertion of Proteins into Membranes • Need to know orientations of the different types of proteins – type I, II, III, and IV (where C-terminal and N-terminal are located – cytosol or exoplasmic space) • All translation is occurring in the cytosol, to get the protein to the membrane it needs a signal • The N-terminal signal sequence is a type of topogenic sequence, form a specific type of shape (topology) • Another type of signal sequence is the SA sequence – signal = go to the ER and the STAsequence – stop transferring to the ER • N-terminal (cleaved) signal sequence • Stop-transfer/membrane anchor sequence (STA) • Signal-anchor - Internal (uncleaved) sequence (SA) • Hydrophobic C-terminus • Tail anchored proteins o Requires Get3 recognition of hydrophobic C-terminal tail, membrane embedded Get1 and 2, andATP hydrolysis o With tail anchored proteins, N-terminal domain is always in the cytosol and the C-terminal domain is always in the ER membrane Insertion of tail-anchored proteins: for C-terminal tail anchored proteins the hydrophobic C-terminus is not available for membrane insertion until protein synthesis is complete and the protein has been released from the ribosome. Step 1: Get3 in anATP-bound state binds to the hydrophobic C-terminal tail. This binding reaction is facilitated by a complex of three proteins (not shown) Step 2: The ternary complex Get3-ATP bound to the C-terminal docks onto the Get1 and Get2 proteins, which are embedded in the ER membrane Step 3:ATP is hydrolyzed andADP is released from Get3, and at the same time, the hydrophobic C-terminal tail is released from Get3 and becomes embedded in the ER membrane Step 4: Get3 binds toATP and Get3-ATP is released from the complex of Get1 and Get2 in a soluble form, ready for another round of binding to a hydrophobic C-terminal tail. Synthesis of Type I Proteins • Have N terminal signal sequence • Have stop-transfer membrane anchor • N-terminal signal sequence signals “take me to the ER”, translation continues and the N-terminal domain goes into the ER lumen and is cleaved off o This is always luminal • Translation continues until it reaches the stop-transfer membrane anchor, which signals a stop o This is always cytoplasmic Synthesis of Type II and Type III Proteins • Have signal-anchor sequence (internal and not cleaved) • Translation starts and N-terminal domain is formed, signal-anchor sequence (transmembrane domain) o If there are positive charges on the N-terminal side, it stays in the cytosol o If there are no charged amino acids, the N-terminal domain moves to the lumen and translocation continues – results in positively charged amino acids on the C-terminal domain (a) Type II proteins Step 1:After the internal signal-anchor sequence is synthesized on a cytosolic ribosome, it is directed to the ER membrane. It becomes oriented in the translocon with its N-terminal portion toward the cytosol. This orientation is mediated by the positively charged residues. Step 2:As the chain is elongated and extruded into the lumen, the internal signal-anchor moves laterally out of the translocon and anchors the chain in the phospholipid bilayer. Step 3: Once protein synthesis is completed, the C-terminus of the polypeptide is released into the lumen and ribosomal subunits are released into the cytosol. (b) Type III proteins Step 1:Assembly is by a similar pathway to that of type II proteins except that positively charged residues on the C- terminal side of the signal-anchor sequence cause transmembrane segment to be oriented within the translocon with its C- terminal portion oriented to the cytosol and the N-terminal side of the protein in the ER lumen Steps 2, 3: Chain elongation of the C-terminal portion of the protein is completed in the cytosol, and ribosomal subunits are released • Orientation determined by positively charged amino acids (kept in cytosol) Synthesis of Type IV Proteins • Has multiple transmembrane domains, also varies in terms of whether the N-terminal domain is in the cytosol or the extracellular space or whether the C-terminal is in the cytosol or the lumen • Orientation of initial helix determined by positively charged amino acids next to signal-anchor sequence • Have alternating signal-anchor sequences and stop transfer sequences • Can have even or odd number of transmembrane domains Topogenic Sequences • Signal, whether it is a internal signal anchor or N-terminal signal anchor, signals to go (translate) to the ER • With this nomenclature, translation is always started at the N- terminal domain • Type I – one transmembrane domain that comes from STA, N-terminal domain in lumen, and C-terminal domain in the cytosol • Type II and II – SAis the transmembrane domain, what about the N-terminal domain? o If there are charges between the N-terminal domain and the SA, N- terminal domain stays in the cytosol, and thus C-terminal will be in the lumen o If there are no charges between the N-terminal domain and the SA, the N-terminal domain goes into the lumen and the rest of the protein stays cytosolic o Charges are cytosolic • Type IVAand
More Less

Related notes for Biology 2382B

Log In


Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.